PROJECT SUMMARY Cardiovascular disease, stroke and cognitive impairment / dementia are leading causes of death and disability, and they arise from several common antecedents. The proposed Vermont Center for Cardiovascular and Brain Health (VCCBH) COBRE at the University of Vermont will address these diseases employing collaborative research. This will be conducted by diverse scientists from multiple disciplines working together to understand the pathobiology and molecular epidemiology of these diseases in order to meet the public health challenges presented by them. The Study Design and Molecular Epidemiology Core (CORE B) of the COBRE will support the evolution of the Center's Project Directors to independent status. It will leverage three decades of experience of the Laboratory for Clinical and Biochemistry Research at the University of Vermont, a leading molecular epidemiology laboratory and home to a biorepository containing ~4.7 million samples from >100,000 research participants from many observational cohort studies and clinical trials. The core will equip the multi- disciplinary Project Directors with the skills they need to conduct their research applying innovative study designs and statistical analyses, and to translate their results from bench or clinical research settings to the population research setting and back, regardless of their prior experience in epidemiology. Our philosophy is that a Core should not only provide service but should train an investigator to be skilled in all of the key elements that the Core provides. Thus, the Core will provide Project Directors with initial and ongoing formal input on their study design and statistical approaches (Aim 1); advise Project Directors on all aspects of biosample procurement, storage, and analysis, including optimizing and troubleshooting assay performance (Aim 2); and support their transition to independence by connecting them with the resources of national studies that will allow them to translate their research to clinical settings (Aim 3). The Core co-directors, Dr. Neil Zakai and Dr. Peter Durda, along with Core biostatisticians, will guide the Project Directors. Dr. Zakai is a hematologist and chronic disease epidemiologist with expertise in many types of study designs, biostatistical approaches to complex data, and laboratory operations, while Dr. Durda has vast experience in molecular laboratory methods and epidemiology. Together, Drs. Zakai and Durda will provide individualized assistance to project directors and innovative workshops utilizing a flipped classroom approach. Services will also be offered to Pilot Grant award recipients who will be supported by institutionally committed funds, to other investigators in the Center's Pipeline development program of potential future Project Directors, and to the UVM research community using a fee-for-service model. Over time the Core will become sustainable, serving the needs of the cardiovascular and neurovascular research community at the University of Vermont.